Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H₂-receptor (H₂R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies.